title: DIXDC1 increases the invasion and migration ability of non-small-cell lung cancer cells via the PI3K-AKT/AP-1 pathway.
abstract: DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a recently identified DIX domain containing protein in zebrafish. DIXDC1 protein was detected in human colorectal adenocarcinoma tissues and was found to be correlated with a high cell proliferation index. We demonstrated DIXDC1 overexpression in 55% (92/167) of non-small cell lung cancer (NSCLC) cases, compared to adjacent noncancerous lung tissues (P < 0.01). Overexpression of DIXDC1 was associated with lymph node metastasis and more advanced TNM stage (P < 0.001 and P = 0.001, respectively). Kaplan-Meier survival curves and log-rank testing indicated that overexpression of DIXDC1 correlated with worse overall survival in NSCLC (P = 0.031). DIXDC1 was more abundant in seven NSCLC lines than the bronchial cell line HBE, and modulation of its expression regulated AP-1 activity; MMP2, MMP7, and MMP9 protein and mRNA; and invasion ability. Metalloproteinase induction was reversed by PI3K/AKT and AP-1 inhibition. These results suggest DIXDC1 is associated with stage and prognosis in NSCLC, and may promote invasion and migration through PI3K-AKT/AP-1-dependent activation of metalloproteinases.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Xu
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.forename: Chuifeng
authors.initials: C
authors.lastname: Fan
authors.forename: Lan
authors.initials: L
authors.lastname: Luan
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002867:Chromones / Q000494:pharmacology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D002867:Chromones; D047908:Intracellular Signaling Peptides and Proteins; D020778:Matrix Metalloproteinase 2; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D008840:Microfilament Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C513335:DIXDC1 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C060932:MMP7 protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human
keywords: AP-1; DIXDC1; PI3K-AKT; metalloproteinases (MMPs); non-small cell lung cancer